Analysis of Ciao1 and Xpd gene functions in Drosophila organ growth

Abstract

Ciao1 is a component of the cytosolic iron-sulfur cluster assembly (CIA) targeting complex along with MMS19 and MIP18. Xeroderma pigemntosum group D (XPD), a DNA helicase involved in regulation of cell cycle and transcription, is a CIA target for iron-sulfur (Fe/S) modification. In vivo function of Ciao1 and Xpd in developing animals has been rarely studied. Here, we reveal that interaction of Crumbs (Crb), Ciao1 and Xpd regulates organ growth in Drosophila. Effects of overexpressing Crb intracellular ($Crb^{intra}$) domain, which is known to promote organ growth by inhibiting Hippo signaling, is suppressed by reducing the Ciao1 level. Loss of Ciao1 critically impairs organ growth. Growth defects caused by Ciao1 RNAi are suppressed by overexpression of Xpd. Remarkably, Xpd RNAi defects can also be suppressed by Ciao1 overexpression, implying a mutual regulation between the two genes. Ciao1 mutant clones in imaginal discs show decreased levels of Cyclin E (CycE). Xpd mutant clones shares the similar CycE reduction. Ciao1 and Xpd are required for normal level of CycE transcription. Further, CycE overexpression is sufficient to restore the growth defects from Ciao1 RNAi and Xpd RNAi. Taken together, this study indicates the role of Ciao1 and Xpd in growth control through regulating CycE expression. Our data also suggests that Crb, Ciao1 and Xpd provide a new pathway for CycE regulation in organ development.